Oxygen-releasing microneedles enhance the therapeutic effect of corneal ectasia by increasing corneal oxygen content and riboflavin concentration during cross-linking

Corneal ectasia, characterized by progressive corneal thinning and reduced biomechanical properties, significantly impairs patients' visual quality. The epithelium-off (epi-off) procedure, the gold standard for treating corneal ectasia, avoids corneal transplantation but can cause pain and delayed healing. In contrast, trans-epithelial therapy preserves the epithelium but suffers from limited riboflavin penetration, reducing its efficacy. Furthermore, corneal cross-linking (CXL) is oxygen-dependent, and rapid oxygen depletion in the corneal stroma significantly limits the CXL efficacy. To alleviate oxygen deficiency in the corneal stroma during CXL, enhance riboflavin penetration, and reduce the side effects of epi-off therapy, novel oxygen-releasing riboflavin microneedles (O₂RF@MNs) are developed. The corneal biomechanical properties of O₂RF@MN_S are 121 % of those of conventional RF@MNs (without oxygen release) and 207 % of the 0.1 % epi-off therapy. Furthermore, corneas treated with O₂RF@MNs show reduced inflammation and pain compared to the epi-off therapy, along with increased riboflavin penetration. Additionally, O₂RF@MNs can mitigate corneal ectasia progression by inhibiting <i>MMP2</i> expression. These findings suggest that O₂RF@MNs represent a promising therapeutic strategy for managing corneal ectasia.